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58 Cards in this Set
- Front
- Back
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Viruses are obligate intercellular parasites T/F
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FALSE, they are obligate intRAcellular parasites, read carefully!
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Most antivirals leave the infected cell in tact T/F
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False
Viruses are absolutely dependent on the metabolic pathways of the host cell for their replication. Hence most agents that block the replication of viruses are also lethal to the cell and therefore unsuitable as drugs |
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Why are viruses unsuitable as drugs?
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Viruses are absolutely dependent on the metabolic pathways of the host cell for their replication. Hence most agents that block the replication of viruses are also lethal to the cell and therefore unsuitable as drugs
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Substances which block the virus replication cycle at various points
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Antiviral drugs
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Many antiviral drugs are 'nucleoside analogues' T/F
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T
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What are nucleoside analogues?
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A range of antiviral products used to prevent viral replication in infected cells
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Give an example of a commonly used nucleoside analogue.
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Acyclovir
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What are the main therapeutic strategies of viruses?
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Inhibition of:
Virus attachment Virus penetration or fusion Virus uncoating (and hence penetration into the host cell Viral DNA polymerase Viral RNA polymers Viral RT Virus maturation (protease inhibitors) Virus release (neuraminidase inhibitors) |
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What kind of enzyme inhibits viral maturation?
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Protease inhibitos
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What kind of enzyme inhibits viral release?
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Neuraminidase inhibitors
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What does a 'neuroaminidase' do?
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It's an enzyme that cleaves the glycosidic linkages of neuraminic acids
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List how viral DNA polymerase is inhibited in herpesvirus
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Learn from sheet
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What is the effect of Acycloguanosine-PPP?
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It inhibits herpesvirus DNA polymerase and thus blocks synthesis of viral DNA
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It inhibits herpesvirus DNA polymerase and thus blocks synthesis of viral DNA
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Acycloguanosine-PPP
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It acts as both an inhibitor and substrate of the viral (herpesvirus) DNA polymerase, competing with GTP and being incorporated into DNA, leading to chain termination
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Acyclovir triphosphate
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Why does acyclovir triphosphate lead to chain termination?
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Because acyclovir lacks the 3'-hydroxyl group required for chain elongation
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When do acyclovir resistant herpesviruses occur?
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When there is a mutation in the herpesvirus thymidine kinase or DNA polymerase
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Most of the drugs used to inhibit viral DNA polymerase are...
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...nucleoside analogues
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What is ganciclovir used for?
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Treating cytomegalovirus infection
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What antiviral is used for treating cytomegalovirus?
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Ganciclovir
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Foscarnet is a _____________ analogue
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A pyrophosphate analogue
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Most drugs used to inhibit viral DNA polymerase are nucleoside analogues, except for...
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Foscarnet, which is a pyrophosphate analogue
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HIV binds to CD7 T/F
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FALSE, binds to CD4!
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HIV binding to CD4 receptor enables it to enter the cell T/F
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False. It needs a co-receptor to enter the cell
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How does inhibition of HIV attachement in the treatment of HIV work?
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In order for HIV to enter cells, it needs to bind to the CD4 receptor on T-cells AND bind to a co-receptor. An inhibitor has been developed that prevents binding to the co-receptor and thus, HIV cannot enter.
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How does inhibition of fusion of the envelope of HIV with the cellular membrane treat HIV?
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A peptide inhibitor stops fusion of the two membranes
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Retroviruses require RT to synthesise DNA from their RNA genome T/F
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T
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RT inhibitors can act against HepB T/F. Why is this strange?
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True. Strange because HepB is a DNA virus, but it has a complex replication cycle involving reverse transcriptase
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What are the two types of RT inhibitors?
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Nucleoside analogue RT inhibitors (NRTIs)
Non-nucleoside RT inhibitors (NNRTIs) |
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Give an example of a NNRTI
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Azidothymidine (AZT)
- Mode of action similar to acyclovir except that all the phosphorylation steps are carried out by host kinases |
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What is the difference between AZT and acyclovir in their action?
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All the phosphorylation steps are carried out by host kinases with AZT
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What is an example of a NNRTI?
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Nevirapine
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What is nevirapine and how does it act?
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It is a NNRTI. The drug binds to RT near to the polymerase active site which becomes distorted with consequent inhibition of enzyme activity (allosteric inhibition)
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The drug binds to RT near to the polymerase active site which becomes distorted with consequent inhibition of enzyme activity (allosteric inhibition)
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Nevirapine
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What is allosteric inhibition?
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The regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site (that is, a site other than the protein's active site)
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What is an allosteric site?
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A site other than the active site of a protein
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How does inhibition of HIV integration work?
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The integrase enzyme is inhibited which prevents proviral DNA formation
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How does inhibition of HIV proteases act as HIV therapy?
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Maturation of the virion - the HIV protease cleaves a polyprotein to produce virus structural proteins. If the enzyme is inhibited by, for example squinavir which mimics the protease's peptide substrate, the newly released virus does not mature and is not infectious
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What is Highly active antiretroviral therapy (HAART) of treating HIV?
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The idea that many drugs are used together at sub-maximal doses (to minimise toxicity).
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How can efficacy of the emergence of resistance in HIV be monitored in HAART therapy of HIV?
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By measuring the amount of viral genome in plasma (viral load)
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What is viral load a measure of?
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The severity of a viral infection
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What are the three drugs used in HAART?
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NRTI
NNRTI Protease inhibitor |
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HAART can eradicate latent HIV T/F
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False
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What are the two methods of influenza therapy?
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Inhibition of virus uncoating and penetration into the host cell
Inhibition of release of influenza virus from an infected cell |
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How does inhibition of virus uncoating and penetration into the host cell method of influenza therapy work?
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Influenza viruses bind to cellular receptors and are then taken up via vesicles (endosomes). IN the acid environment of the endosome, proteins enter the virus allowing uncoating of viral nucleic acid. Amantadine blocks the M2 protein ion transport channel and inhibits uncoating
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What does amantadine do? (Wrt flu virus)
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Blocks the M2 protein ion transport channel and inhibits uncoating
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Blocks the M2 protein ion transport channel and inhibits uncoating
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Amantadine
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Endosome environment is acidic/basic
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Acidic
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What is haemagglutinin?
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A virus attachment protein
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How does the inhibition of release of influenza virus from an infected cell work wrt influenza therapy
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Haemagglutinin binds to salic acid on the cell surface
The flu enzyme, neuraminidase, is essential for release since it removes salic acid from the surface of the infected cell. Neuraminidase inhibitors block release because the haemagglutinin remains bound to sialic acid on the cell surfice |
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What is neuraminidase?
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Essential for release of flu virus
It removes salic acid from the surface of the infected cell |
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What is the function of neuraminidase inhibitors?
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They block release of the flu virus because the haemagglutinin remains bound to sialic acid on the cell surface
0043231110 |
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When are interferons used in viral treatment?
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Treatment in combination with ribavirin (a nucleoside analogue) of some forms of chronic hepatitis (e.g. HepC)
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What is used in combination with interferons to treat HepC?
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Ribavirin
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How do you calculate the therapeutic index wrt viruses? What value should it be?
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Minimum cell toxic dose
/ Minimum virus inhibitory dose Should be at least 10, preferably 10^2-10^3 |
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Why doesn't acyclovir kill host cells?
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Cell Tk doesn't recognise acyclovir
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Which viruses is acyclovir active against?
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HSV and VZV
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What is saquinavir?
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A peptide analogue
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